The following description of the background is provided to aid in understanding the invention, but is not admitted to be, or to describe, prior art to the invention.
Natural nucleos(t)ide compounds are essential molecular building blocks of life and many nucleos(t)ide analog compounds are widely used as antiviral and anticancer agents. Due to the poor lipophilic nature, nucleos(t)ide analog compounds are rarely used as an oral agent. Nucleos(t)ide analog compounds may be used in a form to enhance their oral absorption (e.g., See P. J. Thornton, et al. Journal of Medicinal Chemistry 59:10400-10410 (2016) and J. Rautio, et al. Nature Reviews Drug Discovery 7:255-270 (2008)).
Despite the known nucleos(t)ide analog compounds, there is a need for new compounds with favorable physicochemical, biopharmaceutical or pharmacokinetic properties. For example, liver-targeting compounds which are not active outside the liver reducing pharmacological or toxicological effects of a biologically active agent outside the target tissue. Thus, there is a need for improved liver-targeting compounds in which the compounds remain relatively non-cytotoxic outside the liver.